CBD versus Advil, Motrin, Ibuprofen, and other NSAIDS for Pain and Inflammation

This won't be your surface-level nonsense.

We're going to dive deep into how NSAIDs like Advil works for pain and then compare it with CBD in the same pathways.

Maybe, more importantly, we'll look at the effects on the gut, tolerance, and other important aspects for longer term use.

The gut is the new Rome to where all health roads lead and there's a night and day difference in how Advil affects the gut versus CBD.

This is especially true for autoimmune pain (arthritis, etc).

We'll also dive into headaches and menstrual pains since these three make up the bulk of reasons for people using Advil or Ibuprofen chronically.

Of course, we'll look at the pain pathways directly to see how they differ.

We just wrapped a monster review of CBD and Parkinson's and as expected, gut inflammation and gut barrier breakdown are front and center in the new research.

This new aspect is very important in comparing Advil or Ibuprofen and CBD as you'll see below!

Let's get started...here are the areas we'll cover:

• A quick introduction to the pathways of pain
• How does Advil or Ibuprofen work for pain
• How does CBD work for the pain
• Advil or Ibuprofen versus CBD for the gut barrier and microbiome
• Advil and ibuprofen versus CBD for arthritis
• Advil or Ibuprofen versus CBD for menstrual pain
• Advil and Ibuprofen versus CBD for headaches
• CBD versus Advil, Ibuprofen, NSAIDs for the the liver
• CBD versus Advil, Motrin, and NSAIDS for heart function
• CBD and Advil interactions
• How much CBD for pain relief similar to Advil
• What's the best CBD for pain relief to replace Advil

Here we go…

A quick introduction to the pathways of pain

We first need a lay of the pain landscape to better compare NSAIDs like Advil and Ibuprofen.

We're going to introduce two key pathways:

• Prostaglandins
• COX2

These are very important pain signaling networks that are directly affected by NSAIDs.

The two are interconnected as we'll shortly.

First, prostaglandins.

Prostaglandins come in many flavors but one, in particular, is tied to pain:

Prostaglandin E2 (PGE2) is a well known pain and pro-inflammatory mediator abundantly produced in inflamed tissue

https://pubmed.ncbi.nlm.nih.gov/20666934/

If ever there as a chemical directly tied to the initiation of the pain sensation, it would be this one:

It causes pain by directly exciting nociceptive primary sensory neurons (nociceptors) and indirectly stimulating the release of pain-related peptide substance P (SP) and calcitonin gene-related peptide (CGRP).

https://pubmed.ncbi.nlm.nih.gov/20666934/

It has a range of other functions from controlling muscle and vein dilation to GI movement.

As to our focus...it starts the pain train.

What about COX2?

COX2 is just an upstream agent that drives prostaglandin production!

You may have heard of COX2 inhibitors like Celebrex and Bextra.

They just block this piece to reduce the release of prostaglandins downstream.

So...you stayed with us so far.

Let's get some payback for this time and energy.

How does Advil or Ibuprofen work for pain

First, Advil, Motrin, ibuprofen are all in the same class of drugss.

NSAIDs (non-steroidal anti-inflammatory drugs).

As mentioned above, prostaglandins are inflammatory agents that happen to focus on pain (in the case of PGE2).

So...what's their magic bullet?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for their anti-inflammatory, analgesic, and antipyretic effects. NSAIDs generally work by blocking the production of prostaglandins (PGs) through the inhibition of two cyclooxygenase enzymes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039135/

They reduce prostaglandins via the COX2 control mechanism!

Easy enough.

Research has shown that the opioid system is slightly affected by this prostaglandin effect:

The present results provide evidence that the opioid system participated in the diclofenac and dipyrone-induced peripheral antinociception by indirect activation of κ-opioid receptor probable by release of endogenous opioids such as dynorphins.

https://pubmed.ncbi.nlm.nih.gov/27091501/

Essentially, when they blocked the opioid system, the pain relief of NSAIDs went away.

This makes sense since our opioid system is key to offset pain signals.

As we know more directly from the opioid crisis, chronic fiddling with powerful systems like this can result in tolerance.

In fact, studies are showing this may be the linchpin for NSAID tolerance:

These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341275/

Essentially, the brain areas tied with pain sensation push back against the effect NSAIDs over time.

Your natural pain threshold drops with chronic use not so much because of postaglandin effects but by constantly calling the opioid system into use.

A much slower process as that which happens with opioid sue but minus the spike to dopamine (key to addiction).

Downstream, NSAIDs also reduce other inflammatory agents.

the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1.

https://www.sciencedirect.com/science/article/pii/S0039606016306389

So...in effect...an anti-inflammatory response!

You can see this mirror research that shows a reduction in risk from NSAIDs use during periods of time and later diseases like Alheimers, Autoimmune, etc.

So many diseases are the result of long-term, chronic inflammation.

Let's turn our attention to CBD now.

How does CBD work for the pain

CBD affects many different pathways across the pain spectrum.

We'll cover these areas:

• CBD and neurotransmitters tied to pain
• CBD and glutamate for peripheral pain
• CBD and anandamide for pain
• CBD and prostaglandins
• CBD and COX2
• CBD and the opioid system
• CBD and inflammation tied to pain

Let's start with neurotransmitters...the "pain gaits" in our brain.

CBD and neurotransmitters tied to pain

Pain is actually felt in the brain!

The signal may come from your knee or plantar fasciitis but the sensation is processed in the brain (and spinal cord in tandem).

A big player there is serotonin….our master regulator of all human behavior...including...pain!

There's a great study on CBD's effects following an induced injury with serotonin:

Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/

Let's break this down because it goes to the heart of what we're discussing.

Basically, a painful injury depleted serotonin which led to a state of heightened pain and..anxiety!

Keep in mind that the brain doesn't differ between physical and psychological pain!

Serotonin deals with both equally.

CBD was able to reduce anxiety and heightened pain (hyperalgesia) by "rescuing" serotonin (5HT).

The "rescue" word there is the most important on this page.

It doesn't just boost it in one direction like SSRIs do (see CBD versus SSRIs) but supports it when it's low or depleted (from pain!!).

Check out CBD and serotonin to learn all about this pathway.

Social rejection is treated just the same as a cut by the way!

So serotonin works like a thermostat for how we'll perceive pain and CBD supports it.

Let's look at another player gaining lots of attention...especially in pain syndromes and nerve pain (neuropathy).

CBD and glutamate for peripheral pain

Our nervous system has two powerful players that control basis ebb and flow of activity.

• GABA - our brain's "brake pedal"
• Glutamate - our brain's "gas pedal"

We have multiple systems in place to keep glutamate in discreet range as it's very destructive when too high.

Essentially like redlining an engine but the engine is your brain cell or neuron throughout the body.

This is why pain can get "stuck" on...essentially the pain-sensitive neurons are burnt out and excessive glutamate is the key there.

That's the whole basis behind topical ketamine for pain.

To give a break to the neurons so they can normalize.

The main player holding back glutamate is GABA.

CBD directly supports GABA when it's running low.

Again, it doesn't push it past this point or we would see the same side effects as with benzos (Xanax, Ambien, etc) that boost GABA.

Sedated. Amnesiac. Etc.

CBD is technically called an allosteric negative modulator which is a fancy way to say...a feedback mechanism!

Check out CBD and GABA or CBD and Glutamate to learn more.

CBD primarily does this by supporting Anandamide, our body's natural endocannabnoid:

hese endocannabinoids both act as retrograde messengers on G-protein coupled receptors, are synthesized on demand, and are especially active on glutamatergic and GABA-ergic synapses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/#b6

Let's go there now to understand what was just said!

CBD and anandamide for pain

Anandamide is named after the Hindu goddess of bliss, Anand.

That gives you a good indication of how it feels.

Yes, it's the "high" behind THC or cannabis' effect.

But it's so much more than that especially with pain!

First, is a wet blanket on glutamate activity which is why everything slows down with low levels of THC.

The issue with chronic THC is that it builds tolerance which means your natural anandamide level keeps dropping with use!

Hence, tolerance.

See CBD versus THC to learn more.

What about anandamide and pain?

To put a point to it:

When the body senses pain, anandamide binds to CB-1 and nullifies pain by blocking the signaling.

https://www.scripps.edu/newsandviews/e_20010813/cravatt1.html

Goodness...can we drop the mic?

What about CBD and anandamide?

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/

Remember...pain comes in many forms and excitation or inflammation in the brain is at the core mental health.

CBD does this by blocking FAAH which eats up anandamide.

If you need a powerful example, read our review on the woman who can't feel pain at al ldue to an FAAH gene mutation.

In the future (our guess..next 5-7 years), they will CRSPR the FAAH gene by say...20%...to get rid of chronic pain.

This is one of the most exciting aspects of research happening right now!

Chronic pain will likely not exist 10 years from now.

Anyway, we don't want to boost CB1 activity (where anandamide and THC operate) in one direction chronically or the body will literally reduce CB1 receptor numbers and activity!

This means less pain relief in the future!

It's the basis of tolerance and CBD does not show tolerance in research because it functions in that feedback mechanism we noted above.

By the way, anandamide is key to a range of different pathways in the body as the primary back-up agent for balancing other key pathways.

Check out Endocannabinoid deficiency to learn all about it.

What about prostaglandins, the individual messengers of pain?

CBD and prostaglandins

Let's cut to the chase:

There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol

https://pubmed.ncbi.nlm.nih.gov/14963641/

The free-radicals aspect is interesting.

This is the whole antioxidant aspect.

CBD is actually a more-powerful anti-oxidant than either Vitamin E or C.
We would expect to see this effect with COX since it's in control of prostaglandins.

CBD and COX2

Interestingly, newer research is showing that CBD (and THC) do not directly stimulate COX2 activity at levels that would have an effect.

This is really important for this reason.

The body will routinely use a given pathway for multiple effects depending on the tissue.

There are known knock-on effects from tampering with COX pathways with NSAIDS:

At a time when great concern is accruing in relation to NSAIDs in relation to COX-1 inhibition (gastrointestinal ulcers and bleeding) and COX-2 inhibition (myocardial infarction and cerebrovascular accidents), CBD, like THC, inhibits neither enzyme at pharmacologically relevant doses

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/

So are part of the side effect panel of NSAIDs like Advil:

• GI ulcers and bleeding
• Heart attacks and strokes

Remember how we said COX affects a range of pathways including smooth muscle (like what lines your arteries and heart muscle) and GI function?

If you're chronically suppressing COX activity with NSAIDs, you end up with other issues which is pretty well-known.

CBD can have different effects depending on the state of the system (feedback).

For example, some research shows it can slow down COX in inflammatory states while it's also shown to boost it in cancer cells!

COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells

https://pubmed.ncbi.nlm.nih.gov/23220503/

Apoptosis is how our immune system kills virally infected or cancerous cells.

• This is one of the most telling pieces regarding CBD:
• Healthy cel with low inflammation - CBD does nothing
• Healthy cell with high inflammation - CBD reduces inflammation
• Cancerous or virally infected cell - CBD INCREASES inflammation
• Again, this is how our body naturally kills off cancer.
• Chemo and radiation are gigantic doses of oxidative stress and inflammation essentially.

What about the opioid system?

CBD and the opioid system

Interestingly, CBD is a feedback mechanism in the opioid system as well.

The present study shows that cannabidiol is an allosteric modulator at mu and delta opioid receptors.

https://pubmed.ncbi.nlm.nih.gov/16489449/

Modulator! Not booster like opioids.

This is critical to avoiding the withdrawals created by opioids.

In fact. Even NSAIDs have a long term issue here due to this pathway:

Thus, the mechanism producing tolerance to NSAIDs can be due to the participation of endogenous opioids, endorphins.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341275/

Okay...we've looked at some of the key pain pathways. Let's move further upstream to various systems tied directly with pain.

We'll start with inflammation...the immune system!

CBD and inflammation tied to pain

A whole subset of pain is caused by inflammation.

Inflammation is a powerful tool of our immune system not solely used for dealing with infection, but also for physical damage and repair.

The main types of pain that people routinely take NSAIDs like Advil or Motrin for generally are linked with inflammatory pain.

Arthritis, such as Rheumatoid Arthritis?

Two key pro-inflammatory cytokines in RA are IL-1 and TNFα. Regulation of these cytokines is of crucial importance in the RA disease.

https://www.ncbi.nlm.nih.gov/books/NBK6288/

Cytokines are the little inflammatory assassins of the body that deal with infection and damage.

There's a strong autoimmune angle there which we cover in our CBD and RA or CBD and autoimmune.

What about the standard arthritis...osteoarthritis which generally occurs from injury?

Same thing...just different players:

Here, we first provide a systematic discussion of the known proalgesic effects of cytokines and chemokines that have been detected in osteoarthritic joints, including TNF-α, IL-1, IL-6, IL-15, IL-10, and the chemokines, MCP-1 and fractalkine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254338/

Goodness...it's an alphabet soup of inflammation!

The key word there is "proalgesic"....pain causing!!

COX2, which is directly affected by NSAIDs and CBD, is a powerful inflammatory manager.

These results suggest that COX-2 plays a prominent role in the inflammation associated with adjuvant arthritis and that COX-2 derived PGs upregulate COX-2 and IL-6 expression at inflammatory sites.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/118000/118717/JCI96118717.pdf

Think of it as a dual signaller...pain to us (somethings wrong) and inflammation to the site (something is wrong).

CBD is a powerful antiinflammatory WHEN there is a high inflammation state.

Remember, we don't want to push any pathway solely in one direction or we end up with other problems.

Clinical studies have confirmed that CBD reduces the levels of pro-inflammatory cytokines, inhibits T cell proliferation, induces T cell apoptosis and reduces migration and adhesion of immune cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/

What about the cytokines above from arthritis?

From a study of asthma:

The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.

https://pubmed.ncbi.nlm.nih.gov/26101464/

IL10 happens to be an anti-inflammatory agent!

We have large reviews of CBD and inflammation and even CBD and neuroinflammation.

Speaking of inflammation...let's turn our attention to the gut.

Advil or Ibuprofen versus CBD for the gut barrier and microbiome

This is so important!

All new research is pointing to the gut as a key thermostat for the rest of our body...especially for inflammation.

It's critical for autoimmune, brain health….just about everything.

NSAIDs like Advil or Motrin have an opposite effect to CBD in this realm.

The key consideration is the gut barrier which protects our inner world from the outside world...one teaming with dangerous and opportunistic bacteria and viruses looking to gain entry.

First, NSAIDs:

In addition to gastric damage, NSAIDs are toxic to the intestinal epithelium, causing erosions, perforations, and longitudinal ulcers in the gut.

https://pubmed.ncbi.nlm.nih.gov/29094594/

People...the gut barrier is key to dementia, autoimmune, neuroinflammation, and mental health.

It's now known that NSAIDs break it down.

What about CBD?

Many studies but this one looks at CBD after a really nasty bacteria, C diff (key to hospital superbug) does its damage:

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/

Check out CBD and leaky gut to learn all about it.

As we mentioned above, the gut is a thermostat for the rest of the body for inflammation.

The last thing we want to do is make that trigger worse.

This is a case of NSAIDs (antiinflammatories) actually causing inflammation:

All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.

https://gut.bmj.com/content/43/4/506

As goes the gut, so goes the rest of the body (and brain).

Let's zero in on the main reasons people take NSAIDs.

Advil and ibuprofen versus CBD for arthritis

There are two types of arthritis:

• Autoimmune such as Rheumatoid Arthritis
• Osteoarthritis

Both are inflammatory diseases but with different roots.

NSAIDs definitely have an initial effect of reducing pain, even at levels lower than what is required to bring down inflammation.

For short term use, this is effective.

The issue is with longer term use….a dovetail directly into the nature of arthritis (unless the original injury is fixed).

As we mentioned above, you can build tolerance to NSAIDs.

A study found that this occurred within 4 days after injection directly to the pain center of the brain in animal studies:

Treatment with each NSAID significantly enhanced the tail-flick and hot plate latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, ie, they developed tolerance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505549/

Again, this is the opioid pathway effect.

This means that with long term ue, our natural endorphin production will decrease.

We're losing our safety net.

With rheumatoid arthritis, shoring up gut health is the first key since precedes the disease itself.

As we saw above, NSAIDs will deteriorate the gut barrier while CBD supports it.

Since arthritis is long term, this tolerance effect becomes critical. Learn more at CBD and tolerance.

We have a whole review on CBD and rheumatoid arthritis here.

One note for ladies...Progesterone calms immune response (inflammation) and estrogen supports serotonin (pain threshold).

The aches and pains during hormone flux (cycles, pregnancy, perimenopause) are directly tied to these key pathways.

Let's go there now.

Advil or Ibuprofen versus CBD for menstrual pain

So...what on Earth is going on with menstrual pain and cramping.

Hello Prostaglandins!

Remember how we said the body likes to mix-use different pathways.

Prostaglandins are a key messenger of pain but they also play a vital role in reproduction.

It all starts with progesterone...our masterplanner for pregnancy.

When progesterone drops due to a lack of conception, it signals the cleaning crew to close shop (for that month):

A lower level of progesterone causes a release of acid phosphatase and lytic enzymes present in lysosomes into the cytoplasm. These enzymes digest cells causing the release of prostaglandins.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068519/

Part of this crew is the prostaglandin contingent which starts the inflammatory process needed for the removal of the uterine lining.

Remember...our immune system also governs cell birth and death!

The problem is that these same prostaglandins are also pain signalers downstream.

NSAIDs directly affect this pathway as noted by reducing their levels.

CBD calms this pathway when to heightened. Again, the endocannabinoid system is about balance.

Here's the interesting piece:

Progesterone exposure during the secretory phase (days 12–26 of cycle) is associated with upregulation of endocannabinoid receptors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436335/

Wait a minute. Essentially, when progesterone drops, we lose our endocannabinoid "tone" or base levels.

Our primary "on-call" endocannabinoid is anandamide which has a powerful anti-pain effect.

FAAH breaks it down and CBD eats up FAAH!

See the woman who can't feel pain because of a variant in the FAAH gene.

CBD, essentially, supports anandamide which is what gets knocked down when progesterone leaves the stage!

Interesting right?

The endocannabinoid system is about balance including for the endocrine system (hormones!)

We're getting to the root of the issue (why some women get hit so hard while others don't)...imbalance.

Plus the pain control side (which is just a function of imbalance as well).

Let's look north...to headaches!

Advil and Ibuprofen versus CBD for headaches

Headaches have many causes but many revolve around inflammation and ultimately, expansion or contraction of vascular pathways.

Migraines are actually triggered by a fast dilation of vasculature at the intersection of the brain and spinal cord.

We have a whole review on CBD and migraine along with the powerful effect of magnesium glycinate (especially with visual auras).

We mentioned above that COX pathways are tied to smooth muscle control which is the main mechanism for dilation and constriction of vasculature.

This is fine for short term or as-needed use but long-term tinkering with such a powerful pathway is ill-advised as we'll see in the heart and stroke section below.

We did a full review of CBD and perimenopause migraines (hormones drive all these pathways) but a few takeaways.

Remember how CBD allows for rescue of anandamide activity?

This is very important for migraines with the linchpin of the disease called CGRP:

Several papers from P. Goadsby lab have shown that CGRP-induced dilation of dural blood vessels and neuronal pro-nociceptive activity could be reduced by AEA

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928495/

Remember, migraines start as a vascular issue and then pain follows afterwards.

Headaches really requires a full, detailed exploration which we're planning on now.

Let's turn to the liver.

CBD versus Advil, Ibuprofen, NSAIDs for the the liver

There's a huge difference between CBD and NSAIDs when it comes to the liver.

The liver has the heavy duty role of clearing out NSAIDs from the body since it primarily stays in the blood.

We covered the risk with Tylenol at our CBD versus Tylenol review but NSAIDs are not far behind.

While the major adverse effects of NSAIDs such as gastrointestinal mucosa injury are well known, NSAIDs have also been associated with hepatic side effects ranging from asymptomatic elevations in serum aminotransferase levels and hepatitis with jaundice to fulminant liver failure and death

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820561/

You have less of the liver failure with NSAIDs (compared to Tylenol and its class) but there's definitely a reduction in liver function:

idiosyncratic liver injury due to NSAIDs, transient, mild and asymptomatic elevations in serum aminotransferase levels occur in up to 18% of patients taking NSAIDs over a prolonged period.

https://www.ncbi.nlm.nih.gov/books/NBK548614/

The key there is "Prolonged" time.

What about CBD?

The research we have is how CBD protects the liver against various insults such as heavy alcohol use:

Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608708/

Basically, a systemwide reduction in injury, inflammation, and damage.

Another study on animals following poisoning:

Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057300/

So both liver and brain protection with our favorite word…"normalization".

We look at CBD and blood work to see if there was any effects (none).

The question is...why?

The answer...glutathione!

Glutathione is our primary detox pathway in the body.

The reason Tylenol sends people to the hospital with liver failure is that a metabolite for Tylenol exhausts our glutathione which is a heavy lifter in the liver.

Vitamin C feeds into the glutathione cycle (hence, its importance).

Check out CBD and glutathione or CBD and oxidative stress.

NAC is also a powerful supporter of this pathway and CBD plus NAC could be powerful allies for support with long term NSAID use.

Let's turn to the heart.

CBD versus Advil, Motrin, and NSAIDS for heart function

A known risk with long term NSAID use is heart attack and stroke.

This shouldn't be surprising now that we know the COX pathway governs the lining of our arteries and veins. Smooth muscle control technically.

If you're constantly slamming this pathway, other key controls have to give as well.

Mother nature likes to multi-task!

Blood pressure?

Finally, products of both COX isoforms play a role in the kidney regulating excretion of sodium and water.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422108/

Basically, the kidney manages salt and water to keep blood pressure in a range.

By constantly suppressing COX activity, there's a negative effect with chronic use.

A study looked at calecoxib (Celebrex) to see if would help with heart function and disease.

They found the opposite!:

Unexpectedly, celecoxib treatment led to hallmarks of myofibroblast activation and calcific nodule formation in vitro.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488810/

Myofibroblasts are the precursors to calcification that eventually lines the arteries and can lead to heart attack or stroke.

Remember...COX governs smooth muscle function...the very tissue where this process occurs!

What about CBD and blood pressure and heart function?

First, BP:

CBD reduced resting systolic BP (–6 mmHg; P < 0.05) and stroke volume (–8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470879/

We have a whole review of CBD and blood pressure.

This effect is especially prominent under stress (see CBD and stress for anxiety).

The endocannabinoid system is deeply involved with controlling vasculature health so what is CBD's effect there?:

This study shows, for the first time, that CBD causes vasorelaxation of human mesenteric arteries via activation of CB1 and TRP channels, and is endothelium- and nitric oxide-dependent.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540144/

Essentially, CBD has a calming effect in our arteries and veins with effects both within the wall lining and with nitric oxide, a powerful supporter of heart health.

What about NSAIDs and CBD together?

CBD and NSAIDs or Advil interactions

We don't have good studies that look at this question.

A few points do stand out.

Both CBD and NSAIDs like ibuprofen are metabolized by the p450 pathway in the liver.

For this reason, taking either would likely allow both to remain at higher levels in the blood for longer periods of time.

The general rule is to separate CBD from medications by 4 hours. Peak CBD is around 4-6 hours after taking it.

The range of peak NSAIDs varies significantly with Celebrex having a half-life of 11 hours.

We can use CBD as the determining factor since it's shorter.

Ideally, taken away from each other is standard practice.

Otherwise, CBD may help with some of the negatives of chronic NSAID use from what we've see above.

Normalizing effects such as:

• Rescuing opioid system from NSAID tolerance (see CBD and addiction)
• Liver function and protection
• Gut barrier support and rescue (see CBD and leaky gut)
• Sodium and water effect (kidney function)
• Brain protection
• Glutathione (detox) pathway support (see CBD and glutathione)
• Tissue repair process!

What's the last one?

This is very interesting as it shows there's no free lunch with the body!

NSAIDs are major drugs given after injuries and surgeries related to injuries.

Think of ACL repairs, ankle rolls, etc.

What people don't realize is that our inflammatory response is critical not just for the initial response phase (bruising, swelling, protective tissue, etc) but for the rebuilding process!

Studies have shown that with the short cut of reducing the initial inflammatory response, there's an equivalent reduction in the repair side!

The net effect is higher risk for future injury!

In fact, there is evidence to suggest that long-term use of NSAIDs for managing fracture pain and inflammation carries the risk of impaired bone healing.

https://www.rheumatologynetwork.com/view/do-nsaids-impair-healing-musculoskeletal-injuries

Our inflammatory process controls the matrix or cellular scaffolding and NSAIDs interfere with this (by speeding it up).

CBD has actually been shown to speed bone fracture healing with out the impaired building process:

Taken together, these data show that CBD leads to improvement in fracture healing and demonst

https://pubmed.ncbi.nlm.nih.gov/25801536/

Goodness...see why we get so excited about CBD?

Same theory applies for ligaments and tendons with just less of the mineral that adds "hardness" to organic tissue.

Let's turn to long term use of both.

CBD versus NSAIDs such as Ibuprofen for long term use

We've discussed this quite a bit but for chronic use, NSAIDs are a tough sell for the following reasons:

• Builds tolerance via the opiod system
• Upsets kidney management of salt and water (blood pressure)
• Affects management of smooth muscle (lining in your arteries)
• Dysregulates the repair process for damaged tissue (cartilage, tendons, bones, etc)
• Breaks down the gut barrier

These are all important but the gut barrier and tolerance are the real deal breakers.

The gut barrier is key to inflammatory response across the body with powerful effects on risk for dementia, autoimmune, and mental health.

Tolerance just means that your base level of pain relief and inflammatory response keeps getting ramped down.

This means that NSAIDs will have less effect over time and may even lead to more pain and inflammation with chronic use.

CBD does not build tolerance (see CBD and tolerance).

This is really our favorite piece of CBD and if it weren't true...we would write 1 million plus words on it.

It's really the heart of our fascination since almost all other drugs and even herbal substances push pathways only in one direction.

You need inflammation. You need pain. As we've shown above, inflammation is not all bad!

For chronic use, this "allosteric negative modulator" effect of CBD...feedback mechanism...is the only way to go.

Let's look at some more practical questions.

How much CBD for pain relief similar to Advil or Ibuprofen, etc

We have good research form any other issues including sleep and mental health.

Those levels range from 160 mg (sleep) to 300 mg daily (mental health for neurogenesis).

As for pain, this is really dependent upon your system and nature of pain.

A good process is to start at about 30-50 mg daily (about 1 dropper on the 1000 mg bottle) and test your results.

You can go up from there.

Neuropathy would point more to the 300 mg level since that's critical for BDNF, our nervous system's fertilizer.

For autoimmune and arthritis, this really about gut support and calming inflammatory responses which can range from the 30 up to probably 300 mg.

Again, test how you feel and adjust accordingly knowing that the range is probably 50 - 300 mg daily.

You can hold it under your tongue up to 60 seconds to boost availability and avoid the liver breaking it down.

After a fatty meal is best and you can break it up into different doses.

Then, the question of what type of CBD?

What's the best CBD for pain relief to replace Advil

There are some basic requirements with CBD:

• Organically grown in the US at FDA registered farms
• CO2 processed
• 3rd party tested
• No THC
• No heavy metals
• No solvents
• No pesticides
• No mold
• No bacteria

You can find our testing at the top of any page.

Then there's the question of CBD isolate versus full spectrum.

Most of the market is pushing full spectrum even though all the research is on CBD isolate by itself.

The bigger issue is histamine response.

40-60% of the population has histamine issues and this goes up as we get older and for women (progesterone leaving).

That's an interesting correlation with pain issues (arthritis, etc).

The last thing we want to do is spike histamine response from all the plant material in full spectrum CBD:

In the PNS, histamine is released in response to tissue injury/damage, and, through the sensitization of polymodal nociceptors resulting in increased firing rates, it contributes to the generation of pain hypersensitivity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012972/

Histamine is a powerful signalling agent in its own right with pain...especially throughout the body's nervous system.

There's lot so research on CBD isolate calming histamine response (see CBD and histamine or CBD and mast cell activation).

The side effect profile reported by our customers is night and day between isolate and full spectrum (see reviews on product pages) and we found isolate after histamine responses to full spectrum when we first started this journey.

Then, there's cost.

The key there is cost per mg of CBD.

We price our 6000 mg bottles at 2-3 cents before discount up to 50% for this reason.

With research pointing to 100-300 mg for pain, affordability is critical.

Afterall, we found CBD due to a brutal perimenopause so we want to make sure it's available for people suffering.

Be well. Take care of each other. Take care of yourself!

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.